EndoS and SpeB from Streptococcus pyogenes Inhibit

The human pathogen Streptococcus pyogenes primarily infects the upper respiratory tract and skin, but oc-casionally it disseminates and causes severe invasive disease with high mortality. This study revealed that the activity of extracellular EndoS, which hydrolyzes the functionally important N-linked oligosaccharides on op-sonizing immunoglobulin G (IgG), contributes to increased survival of S. pyogenes in human blood ex vivo. The inability to kill the bacteria is due to reduced binding of IgG to Fc receptors and impaired classical pathway-mediated activation of complement. In addition, the activity of extracellular SpeB, which cleaves IgG into Fc and Fab fragments, also increases bacterial survival. This suggests that S. pyogenes expresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system. A prerequisite for a pathogen to successfully invade and colonize a host is to escape recognition by the immune system. Many host defense mechanisms are involved in the battle against bacterial infections, and two significant events are op-sonization and phagocytosis. These events involve antigen rec-ognition, complement deposition, and phagocytic cells that engulf and kill the microorganism after recognition by hos